Gas chromatography-olfactometry-mass spectrometry (GC-O-MS) is a combination of gas chromatography-olfactometry (GC-O) and gas chromatography-mass spectrometry (GC-MS). GC-O-MS technique is a powerful tool to study food flavors and it has been widely applied for aroma and flavor analysis of various food items. In combination with different technologies, GC-O-MS can be applied to solve many flavor problems in the food industry such as quick mapping of aroma-active compounds, identification of key aroma-active compounds, cluster analysis based on the aroma-active compounds, relationship between odorants and sensory properties, and clarification of formation mechanism of important odorants. The newly proposed "molecular sensory science" concept (or sensory-directed flavor analysis) provides a much deeper research for the GC-O-MS application. Here, we have reviewed the operation, advantages and applications of GC-O-MS technique. Qualitative/quantitative analysis methods and sampling methods of aroma-active compounds have been described to introduce the different application areas of GC-O-MS. Case studies based on existing papers and our research have been discussed.